Keywords
immature teratoma - submandibular gland - infant - case report
Introduction
Extragonadal germ cell tumors (EGTs) are developed outside the gonads and histologically classified into seminoma/nonseminoma and mixed tumors.[1] Except for morphological similarities, EGTs themselves have substantially different biology than their gonadal counterparts. Teratomas generally have one or more embryonic layers that differentiate into identifiable tissues and organs in unusual sites and ectopic locations.[2] Mature teratomas are occasionally observed to experience malignant transformation and necessitate extended monitoring.[3] Immature teratomas, particularly extragonadal ones located in unusual sites, are exceedingly rare. To our knowledge, this can be the first case documented globally. Hence, we report this case of an immature teratoma of the right submandibular gland in an infant.
Case Report
A 3-month-old baby was brought to our facility with right cervical swelling, evident 1 month after birth. The swelling was progressive with no accompanying fever or any other symptoms. On examination, the swelling was well circumscribed, confined to the submandibular gland, soft in consistency, measuring grossly 5 × 3 × 1.5 cm in greatest dimension. Head and neck (H&N) MRI revealed a well-defined right submandibular gland lesion of mixed components. USG-guided fine needle aspiration cytology of the swelling was done, and it was reported to be negative for malignancy. Since it was present almost since birth, we assumed it to be a case of cystic hygroma and opted for surgery.
Intraoperatively, the lesion was well encapsulated ([Fig. 1A]) and the lesion with the gland was excised in toto. The bed was clean after achieving hemostasis ([Fig. 1B]). The defect was closed primarily ([Fig. 1C]). The postoperative healing was uneventful.
Fig. 1 (A) Well-encapsulated lesion with submandibular gland, (B) defect after surgical excision, (C) closure done in layers, (D) laryngeal prominence (LP) view of the thyroid, (E) LP view of an immature neuroepithelium, (F) LP view of the intestinal epithelium, (G) LP view of the neuroparenchyma, (H) LP view of cartilage, (I) immunohistochemistry (IHC) showing positivity for p63, (J) IHC showing positivity for PLAP, (K) IHC showing positivity for S100, (L) IHC showing positivity for TTF1, and (M) IHC showing negativity for alpha fetoprotein (AFP).
However, postoperatively, the histopathology report sections from the lesion showed a tumor comprising of components of all three germ layers comprising neuronal tissue, cartilage, thyroid tissue, intestinal epithelium, and bronchial and squamous epithelium. An immature component in the form of neuroectodermal tissue was seen arranged in a rosette pattern. All the features were suggestive of grade 2 immature teratoma ([Fig. 1D–H]). Immunohistochemistry was advised and it was positive for placental alkaline phosphatase (PLAP), OCT2, P63, vimentin, TTF1, and S100 ([Fig. 1I–L]) and negative for alpha fetoprotein (AFP; [Fig. 1M]), SALL4, and glypican 3, reconfirming the histopathology report of grade 2 immature teratoma. Serum markers beta-human chorionic gonadotropin (Beta HCG), and lactate dehydrogenase (LDH) were normal. Serum AFP was 51.1 IU/mL, which is deemed normal in this age range. A full-body PET-CT scan was performed, and it showed no fluorodeoxyglucose (FDG) avidity anywhere else in the body. The patient's relatives were unwilling to any further systemic therapy and close surveillance was advised. At 6 months postoperatively, the baby is doing well with no evidence of disease with progressively decreasing AFP values.
Discussion
Pediatric germ cell tumors have a similar biology to that of adults with respect to the expressions of beta HCC and AFP, which are useful in predicting response, relapse, and prognosis.[4]
[5] However, one important aspect that has to be kept in mind is that in the newborn the AFP levels are 5,000 ng/mL and it will take up to 6 months for these level to fall to less than 20 ng/mL (normal adult value).[6] Hence, treatment decisions in infants should not be taken alone by observing the AFP levels. Literature strongly indicates the need for regular imaging and follow-ups instead of relying solely on the AFP levels, even for patients who have undergone surgery.[7]
Dharmarajan et al. and colleagues in their review also highlighted the rarity of H&N teratomas (∼6%) among the other teratomas of the region.[7] The prominent teratomas were reported to be in the neck and oropharynx, followed by the nasopharynx.[8] As teratomas are rare and cervical teratomas may mimic other neck masses on initial presentation, a differential diagnostic workup should be done to rule out these. Most cervical teratomas in younger patients are typically benign, but as individuals age, the likelihood of these tumors being malignant increases proportionally. Cervical teratomas, depending on their location and size, may sometimes be catastrophic with a prenatal mortality rate greater than 80% due to airway obstruction, inadequate fetal swallowing, and feeding issues at delivery.[8]
[9] So, the survival of such infants with immature teratomas primarily hinges on prompt diagnosis and treatment. Prenatal evaluation can aid in strategizing airway control during delivery by ensuring the proper airway control through the execution of an operation on placenta support (OOPS) and ex utero intrapartum treatment.[9]
[10]
Postpartum, if left untreated, such infants typically have poor prognosis with a significant risk of mortality up to 90 to 100%.[10] If treated promptly, the 5-year survival rates have been indicated to exceed 80%.[11]
[12] Continuous long-term monitoring, regular follow-up, and remaining alert must be upheld regardless of the resection and its outcomes.[7]
To date, no set clinical management guidelines or chemo protocols are available to treat immature teratomas in infants.[10] Surgical excision was always considered the treatment of choice. However, a combination of surgery followed by chemotherapy was observed to have better prognosis and survival (98.6%), especially in extracranial immature teratomas.[13]
Reports suggest that adjuvant chemotherapy or radiotherapy is redundant in infants due to associated risks, unless the teratomas are invasive, disseminated, and with residual disease.[14]
[15] The role of tumor markers such as AFP are not at par compared to the conventional methods such as imaging and clinical assessments in assessing prognosis and detecting tumor recurrence.[7] Overall, a multifaceted clinical strategy was observed to be beneficial.
Conclusion
This is the first documented case of an immature teratoma located in the right submandibular gland of an infant. Early intervention and resection can reduce the morbidity and mortality rate to a minimum, providing better survival. In exceptional cases, these tumors can give rise to airway obstruction, where complete surgical resection of the tumor is the treatment of choice. Overall, early imaging, differential diagnosis, and multidisciplinary clinical management have proven beneficial for better prognosis.
